title: Intramyocardial plasmid-encoding human vascular endothelial growth factor A165/basic fibroblast growth factor therapy using percutaneous transcatheter approach in patients with refractory coronary artery disease (VIF-CAD).
abstract: BACKGROUND
  VIF-CAD randomized, placebo-controlled, double-blind trial was an attempt to induce therapeutic angiogenesis by percutaneous intramyocardial transfer of bicistronic (vascular endothelial growth factor/fibroblast growth factor [VEGF/FGF]) plasmid (pVIF) in patients with refractory heart ischemia. Myocardial perfusion, clinical symptoms, exercise tolerance, left ventricular function, and safety were assessed.
  
  
  METHODS
  Fifty-two patients with refractory coronary artery disease were randomized to receive VEGF/FGF plasmid (n = 33) or placebo plasmid (n = 19) into myocardial region showing stress-induced perfusion defects. Repeat stress and rest technetium Tc 99m sestamibi single-photon emission computed tomography at 5 months was the primary efficacy measure. Secondary assessment included Canadian Cardiovascular Society class and exercise tolerance at 5 and 12 months.
  
  
  RESULTS
  Rest- and stress-induced perfusion defects did not differ between groups. Canadian Cardiovascular Society functional class improved after 5 (P = .0210) and 12 months (P = .0607) in the treatment group. The exercise tolerance of treated patients improved: total exercise time increased marginally (P = .0541); maximum workload (P = .0419) and total test distance (P = .0473) increased significantly, compared to placebo.
  
  
  CONCLUSIONS
  Bicistronic VEGF/FGF plasmid therapy did not improve myocardial perfusion measured by single-photon emission computed tomography. However, treated patients experienced improvement with respect to exercise tolerance and clinical symptoms. Intramyocardial VEGF/FGF bicistronic plasmid transfer seemed safe throughout the follow-up period of 1 year.
authors.affiliation: Institute of Cardiology, Warsaw, Poland. kkukula@ikard.pl
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kukuła
authors.forename: Lidia
authors.initials: L
authors.lastname: Chojnowska
authors.forename: Maciej
authors.initials: M
authors.lastname: Dąbrowski
authors.forename: Adam
authors.initials: A
authors.lastname: Witkowski
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Chmielak
authors.forename: Mirosław
authors.initials: M
authors.lastname: Skwarek
authors.forename: Jacek
authors.initials: J
authors.lastname: Kądziela
authors.forename: Anna
authors.initials: A
authors.lastname: Teresińska
authors.forename: Maciej
authors.initials: M
authors.lastname: Małecki
authors.forename: Przemysław
authors.initials: P
authors.lastname: Janik
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Lewandowski
authors.forename: Mariusz
authors.initials: M
authors.lastname: Kłopotowski
authors.forename: Jacek
authors.initials: J
authors.lastname: Wnuk
authors.forename: Witold
authors.initials: W
authors.lastname: Rużyłło
mesh_terms: D000368:Aged; D005080:Exercise Test; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000628:therapy*; D018919:Neovascularization, Physiologic; D010957:Plasmids; D019275:Radiopharmaceuticals; D017256:Technetium Tc 99m Sestamibi; D015899:Tomography, Emission-Computed, Single-Photon; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000502:physiology / Q000627:therapeutic use*
chemical_list: D019275:Radiopharmaceuticals; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D017256:Technetium Tc 99m Sestamibi